Table 4 A review of the literature and databases on the known variants of the ZDHHC9 gene

NM_016032.3(ZDHHC9): c.145T > C

Missense

p.Cys49Arg

Pathogenic

Not Provided

N/R^*

N/R

N/R

N/R

N/R

N/R

N/R

-

Hu (2016) Mol Psychiatry 21, 133 [22]

NM_016032.4(ZDHHC9):c.251T > C

Missense

p.Leu84Ser

Likely Pathogenic

Not Provided

N/R

N/R

N/R

N/R

N/R

N/R

N/R

-

ClinVar (RCV000484510.1)

NM_016032.4(ZDHHC9):c.268G > A

Missense

p.Asp90Asn

Likely Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type

N/R

N/R

N/R

N/R

N/R

N/R

N/R

-

ClinVar (RCV000760177.1)

NM_016032.4(ZDHHC9):c.286C > T

Missense

p.Arg96Trp

Pathogenic/Likely Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type

Yes

N/R

N/R

Yes

N/R

N/R

N/R

Global Developmental Delays without Marfanoid habitus, Structural Brain Abnormalities

Tzschach (2015) Eur J Hum Genet 23 [17]

NM_016032.4(ZDHHC9):c.442C > T

Patient 1

Missense

p.Arg148Trp

Pathogenic/Likely Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type, Intellectual Disability

Yes

N/R

Yes

N/R

N/R

Yes

N/R

Developmental Delay, Mild Fixed Flexion Deformity at the Elbows, Large Ears, Long Fingers and Toes, Pes Planus

Raymond (2007) Am J Hum Genet 80, 982

[23]

Patient 2

Developmental Delay, Large Ears, Long Fingers and Toes, Pes Planus

NM_016032.4(ZDHHC9):c.448C > T

Missense

p.Pro150Ser

Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type

Yes

N/R

Yes

N/R

N/R

N/R

N/R

Joint Hypermobility, Pectus Excavatum, Long Digits, Delayed Sitting, Adducted Thumbs at Birth that resolved spontaneously, Long Face, Strabismus, Prominent Ears, Long, Thin Limbs, 5th-Finger Camptodactyly, Long Toes with Camptodactyly

Raymond (2007) Am J Hum Genet 80, 982

[23]

NM_016032.4(ZDHHC9):c.496G > A

Missense

p.Asp166Asn

Likely Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type

N/R

N/R

N/R

N/R

N/R

N/R

N/R

-

ClinVar (RCV001754546.1)

NM_016032.3( ZDHHC9): c.892C > T

Missense

p.Arg298Gln

Pathogenic

Moderate Intellectual Disability with Speech Delay

Yes

Yes

N/R

Yes

N/R

N/R

N/R

MRI Brain: Retro-Cerebellar CSF Fluid Collection

Bowling (2017) Genome Med 9, 43 [24]

NM_016032.3( ZDHHC9): c.892C > T

Nonsense

p.Arg298*

Pathogenic

Intellectual Disability

Yes

N/R

N/R

N/R

N/R

N/R

Yes

Limited Extension of the Elbows and Metacarpophalangeal Joints, Acrocyanosis, Dysplastic Corpus Callosum, Lingual Fasciculation

Masurel-Paulet (2014) Am J Med Genet A 164, 789

[25]

NM_016032.4(ZDHHC9):c.167 + 5G > C

Patient 1

Splicing

p.Thr11Profs833

Pathogenic

Not Provided

Yes

Yes

Yes

N/R

N/R

Yes

Yes

Developmental Delay, Pectus Carinatum, Pes Planus, Thin Facial Features

Raymond (2007) Am J Hum Genet 80, 982

[23]

Patient 2

NM_016032.3 ( ZDHHC9):c.172-175dup

1 (Two sibs)

Splicing

p.Tyr59Serfs*33

Pathogenic

Not Provided

Yes

Yes

N/R

N/R

Yes

N/R

N/R

Developmental Delay and Moderate Learning Disability, a High Forehead, Severe Constipation, Hypertelorism

Raymond (2007) Am J Hum Genet 80, 982

[23]

2 (Maternal uncle)

No Walking, Need Full-Time Care

NM_016032.3( ZDHHC9):c.361C > T

Missense

p.(Arg121Ter)

Likely Pathogenic

Not Provided

N/R

N/R

N/R

N/R

N/R

N/R

N/R

-

LovD3 (https://databases.lovd.nl/shared/variants/ZDHHC9/unique)

NM_016032.3( ZDHHC9): c.878_879insA

Frameshift (Small Insertion)

p.Ser294Glnfs*26

Likely Pathogenic

Not Provided

Yes

N/R

N/R

N/R

N/R

N/R

N/R

-

Grozeva (2015) Hum Mutat 36, 1197 [26]

NM_016032.4(ZDHHC9):c.777 + 1G > A

Splicing

-

Likely Pathogenic

Abnormality of the Nervous System

N/R

N/R

N/R

N/R

N/R

N/R

N/R

-

Retterer (2016) Genet Med 18, 696

NM_016032.3 (ZDHHC9):c.487 + 5_487 + 19del

Small Deletion

-

Likely Pathogenic

Not Provided

Yes

N/R

N/R

N/R

N/R

N/R

N/R

Global Developmental Delay, Gait Ataxia, Macrotia, High Narrow Palate, Hypertonia, Hyperreflexia

Anazi (2017) Hum Genet 136, 1419

[27]

6-31kb DEL, EX10-11DEL

Gross Deletion

-

Pathogenic

Mental Retardation, X-linked

Yes

N/R

N/R

N/R

N/R

N/R

N/R

-

Boone (2010) Hum Mutat 31, 1326 [28]

2-KB DEL, EX6-7DEL

Gross Deletion

-

Pathogenic

Intellectual Disability

Yes

No

N/R

N/R

Yes

N/R

Elongated and Down‐Slanting Palpebral Fissures and High Hairline

Schirwani (2018) Am J Med Genet A 176, 1238 [29]

Insertion of 4.68Mb

Gross Insertion

-

Likely Pathogenic

Not Provided

Yes

N/R

N/R

N/R

N/R

N/R

N/R

Short Stature, Microcephaly

Willemsen (2012) Eur J Med Genet 55, 586

[30]

NM_016032.4 (ZDHHC9): c.566T > C

1 (proband)

Missense

p.Leu189Pro

Likely Pathogenic

Syndromic X-Linked Intellectual Disability Raymond Type

Yes

Yes

No

No

No

No

No

Developmental Delay, Vision Problem (in older brother and maternal uncle), Muscular Weakness (in older brother), Brain Tumor (in proband)

Current Study

2 (older brother)

3 (maternal uncle)